Parkinson's Disease - Levadopa (L-dopa)

Reasons for the Wearing-Off Effect. Debate is ongoing about the cause of the wearing-off effect and dyskinesia. Some theories suggested for these effects are the following:

• The disease progresses beyond the ability of levodopa to control it.
• Some patients become tolerant to prolonged exposure to dopamine and, at the same time, the disease is progressing.
• The brain's own dopamine neurons become incapable of storing dopamine and when the levodopa wears off, little or no natural dopamine remains.
• Levodopa itself accelerates the disease by producing oxygen free radicals, unstable particles that increase injuries to the brain and dopamine degradation.

Preventing the Wearing-Off Effect. To reduce the effects of fluctuation and the wearing-off effect, it is important to maintain as consistent a level of dopamine as possible. Unfortunately, levodopa is poorly absorbed and may remain in the stomach a long time. A number of strategies are being developed to take care of these problems:

• Some patients take multiple small doses on an empty stomach, crushing the pills and mixing them with a lot of liquid.
• A liquid form of Sinemet may produce fewer fluctuations and a prolonged "on" time compared with the tablet.
• A prolonged release version of levodopa and carbidopa (Sinemet CR) is also available to control fluctuations for some people. (Some evidence suggests that there is no actual difference in symptom control between the sustained and immediate release forms, but patients on Sinemet CR tend to experience a better quality of life.)

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